When an immune response is desired to a particular antigen or hapten, it may be necessary to supplement the administration of the hapten with a material which enhances its ability to elicit either or both a B-cell mediated or T-cell mediated response. One general class of such supplementing agents has generally been classified as adjuvants. These are materials administered along with the hapten which seem to aid in securing the desired response. The use of killed bacteria and the products thereof as such adjuvants has a considerable history, and the use of Freund's Complete Adjuvant (killed Mycobacteria) or other bacteria and their components such as peptidoglycan as immunomodulators has been reviewed, for example, by Warren, H. S., et al., Ann Rev Immunol (1986) 4:369. Naked or acid-treated bacteria have also been shown to act as adjuvants to induce humoral immunity to carbohydrate moieties on large glycoproteins by Bellstedt, D. U., et al., J Immunol Meth (1987) 98:249-255; Livingston, P. O., et al., J Immunol (1987) 138:1524-1529.
European patent application publication No. 180,564 describes the preparation of a complex from bacterial substrates designated "Iscom." This complex is prepared by solubilizing the hydrophobic peptides from bacteria into detergent, removing the detergent from the solubilized material and replacing it with glycosides, such as saponin.
Haptens which are contained in small molecules, especially carbohydrates, are also rendered more immunogenic by conjugation to a carrier such as bovine serum albumin, keyhole limpet hemocyanin, diphtheria or tetanus toxoids and the like. The resulting conjugate vaccination antigens possess increased immunogenic potential with respect to the low-molecular weight haptens.
Finally, the immune response to weak immunogens, such as carbohydrate antigens, is usually an antibody response, mediated by B-lymphocytes, whereas effective protection through vaccination would generally require participation of T-lymphocytes in the immune response. To modulate the immune response to carbohydrate haptens in favor of T-lymphocyte-mediated immunity, is another reason why B-lymphocyte-dependent haptens have been attached to protein carriers.
Depending on the nature of chemical linking process chosen, such binding of haptens to carriers is often poorly defined and poorly reproducible. Also, where the carriers are toxoids such as diphtheria or tetanus toxoids, their formation from the corresponding toxins is sometimes incomplete so that toxoid preparations show residual toxic activity.
The invention provides two-dimensional crystalline carriers which permit definition of these parameters so that an ordered structure bearing the immunostimulatory or immunoregulatory substance can be obtained, and problems associated with toxicity are minimized.